Researchers have long believed that diabetes begins when the immune system attacks insulin-producing beta cells in the pancreas. But by investigating beta cells’ complex biology, researchers at the University of California-San Francisco Diabetes Center made a discovery that could prevent the onset of the disease in people who are at high risk.
By studying non-obese diabetic mice, the team found that beta cells experience “secretory senescence,” where DNA damage causes them to stop working properly. The beta cells then harm neighboring cells, causing the immune system to start attacking the whole insulin-producing system, namely the beta cells.
In addition, they found that Venclexta (AbbVie), which is FDA-approved to treat leukemia, can prevent the onset of diabetes in mouse models.
To discover whether their findings might translate to people, the researchers studied beta cells from six people with early-stage diabetes and six healthy donors. Those who had been diagnosed with diabetes showed clear signs of secretory senescence. Beta cell senescence also showed up in those who had not been diagnosed with diabetes but were considered at high risk as their blood tests showed early signs of an immune reaction to beta cells.
To find out whether eliminating senescent cells can prevent type-1 diabetes, the researchers used Venclexta, which targets senescent cells but leaves healthy tissues intact.
When they gave the drug to mice predisposed to diabetes for two weeks prior to disease onset, only 30% developed symptoms versus 75% of mice who didn’t receive the medicine. Further, they discovered that Venclexta had eliminated the senescent cells and left the healthy beta cells intact.
Source: FierceBiotech, February 22, 2019